Fig 1.
Surface recruitment of human proteins by Strep A.
Left, Schematic of the M protein coiled coil attached covalently to the Strep A cell wall. The N-terminal 50 amino acids of mature M protein define its type (cyan), and the N-terminal third to half of M protein is sequence variable (orange). Right, M and M-like proteins on the Strep A surface recruit C4BP, FH, Fg, and Pla to block the deposition of opsonins, such as C3b and antigen-specific antibodies. M and M-like proteins also interact with IgG and IgA in nonimmune fashion through their Fc domains. C4BP, C4b-binding protein; Fc, fragment crystallizable; Fg, fibrinogen; FH, factor H; IgA, immunoglobulin A; IgG, immunoglobulin G; Pla, plasminogen.
Fig 2.
(A) S-region binding motif for Fcγ-binding. Top, the sequence of the M1 protein S-region is aligned with the S-region motif in Mrp4. Amino acids that occupy a or d positions of the coiled coil heptad repeat in the structure of the M1 S-region are denoted above the sequence and enclosed in red boxes. Bottom, coiled-coil propensity of the M1 protein S-region. (B) Structure of the M1 protein S-region (red) in cartoon representation. The B-repeats region of M1 protein is in cyan and fibrinogen fragment D in gray. (C) Top, G1234 and EQ-rich motifs for Fcγ-binding from M2 protein. Bottom, coiled-coil propensity of the sequence at top. (D) Top, Fcα-binding motif from M4 protein. Bottom, coiled-coil propensity of the sequence at top.
Fig 3.
Structure of IgG1 (PDB 1IGY), left, and IgA-Fc1 (PDB 2QEJ), right, in cartoon representation. The interfaces between the CH2 (blue) and CH3 (red) domains are indicated by arrows.
Fig 4.
M and M-like protein coiled coils are often unstable at 37°C but can be stabilized by the low-affinity binding (denoted by thin arrows) of a ligand (circle or triangle). Formation of coiled-coil structure promotes the high-affinity interaction (denoted by thick arrows) of a second ligand.